drugset / Trial / NCT01764633
Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk
RandomizedParallel-groupQuadruple-blindTreatment
Summary
The primary objective was to evaluate the effect of treatment with evolocumab, compared with placebo, on the risk for cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization, whichever occurs first, in patients with clinically evident cardiovascular disease.
Timeline
- Start
- 2013-02-08
- Primary completion
- 2016-11-11
- Completion
- 2016-11-11
Outcome
Met primary endpoint
registry analysis (superiority test); Placebo vs Evolocumab; p < 0.0001; Hazard Ratio (HR) 0.85 (95% CI 0.79 to 0.92); Log Rank NCT01764633 ↗
release “Data from a Phase 3 study evaluating the effects of Repatha on cardiovascular outcomes that met its primary composite endpoint and key secondary composite endpoint” amgen.com ↗
release “Results from the first completed large cardiovascular outcomes trial (FOURIER) were reported in March 2017 . Repatha® (evolocumab) significantly reduced the risk of cardiovascular events.” alnylam.com ↗
release “The study in approximately 27,000 subjects with clinically evident ASCVD met its primary composite endpoint” alnylam.com ↗
release “The FOURIER trial recently showed that Repatha reduced major CV events compared to placebo in high-risk CV patients” amgen.com ↗
release “The study found a statistically significant 15 percent reduction ( p <0.001) in the risk of the primary composite endpoint” amgen.com ↗
release “The study found a statistically significant 15 percent reduction ( p <0.001) in the risk of the primary composite endpoint” amgen.com ↗
release “The study found a statistically significant 15 percent reduction (p <0.001) in the risk of the primary composite endpoint” amgen.com ↗
Publications
- Background Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17.
- Background Fonarow GC, Keech AC, Pedersen TR, Giugliano RP, Sever PS, Lindgren P, van Hout B, Villa G, Qian Y, Somaratne R, Sabatine MS. Cost-effectiveness of Evolocumab Therapy for Reducing Cardiovascular Events in Patients With Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2017 Oct 1;2(10):1069-1078. doi: 10.1001/jamacardio.2017.2762.
- Background Fonarow GC, van Hout B, Villa G, Arellano J, Lindgren P. Updated Cost-effectiveness Analysis of Evolocumab in Patients With Very High-risk Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2019 Jul 1;4(7):691-695. doi: 10.1001/jamacardio.2019.1647.
- Background Schludi B, Giugliano RP, Sabatine MS, Raal FJ, Teramoto T, Koren MJ, Stein EA, Wang H, Monsalvo ML. Time-averaged low-density lipoprotein cholesterol lowering with evolocumab: Pooled analysis of phase 2 trials. J Clin Lipidol. 2022 Jul-Aug;16(4):538-543. doi: 10.1016/j.jacl.2022.05.069. Epub 2022 Jun 6.
- Background Berg DD, Moura FA, Bellavia A, Scirica BM, Wiviott SD, Bhatt DL, Raz I, Bohula EA, Giugliano RP, Park JG, Feinberg MW, Braunwald E, Morrow DA, Sabatine MS. Assessment of Atherothrombotic Risk in Patients With Type 2 Diabetes Mellitus. J Am Coll Cardiol. 2023 Jun 27;81(25):2391-2402. doi: 10.1016/j.jacc.2023.04.031.
- Background Clinical Benefit of Evolocumab Treatment Among Patients With Atherosclerotic Cardiovascular Disease: Exploration Based on the Chinese Subgroup of FOURIER Study, ZHANG Lihua1 , LI Weimin2 , YAO Zhuhua3 , CHEN Jiyan4 , DONG Jun5 , LI Jing1 (Chinese Circulation Journal, 2023, 38: 704.)
- Monguillon V, Kelly PJ, O'Donoghue ML, Park JG, Bohula EA, Saver JL, Atar D, Keech AC, Sever PS, Wang H, Paiva da Silva Lima G, Sabatine MS, Giugliano RP. Efficacy and Safety of Very Low Achieved LDL Cholesterol in Patients With Previous Ischemic Stroke. Circulation. 2026 Jan 13;153(2):86-93. doi: 10.1161/CIRCULATIONAHA.125.077549. Epub 2025 Nov 3.
- Zimerman A, Kunzler ALF, Weber BN, Ran X, Murphy SA, Wang H, Honarpour N, Keech AC, Sever PS, Sabatine MS, Giugliano RP. Intensive Lowering of LDL Cholesterol Levels With Evolocumab in Autoimmune or Inflammatory Diseases: An Analysis of the FOURIER Trial. Circulation. 2025 May 20;151(20):1467-1476. doi: 10.1161/CIRCULATIONAHA.124.072756. Epub 2025 Apr 21.
- Gaba P, O'Donoghue ML, Park JG, Wiviott SD, Atar D, Kuder JF, Im K, Murphy SA, De Ferrari GM, Gaciong ZA, Toth K, Gouni-Berthold I, Lopez-Miranda J, Schiele F, Mach F, Flores-Arredondo JH, Lopez JAG, Elliott-Davey M, Wang B, Monsalvo ML, Abbasi S, Giugliano RP, Sabatine MS. Association Between Achieved Low-Density Lipoprotein Cholesterol Levels and Long-Term Cardiovascular and Safety Outcomes: An Analysis of FOURIER-OLE. Circulation. 2023 Apr 18;147(16):1192-1203. doi: 10.1161/CIRCULATIONAHA.122.063399. Epub 2023 Feb 13.
- Erviti J, Wright J, Bassett K, Ben-Eltriki M, Jauca C, Saiz LC, Leache L, Gutierrez-Valencia M, Perry TL. Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data. BMJ Open. 2022 Dec 30;12(12):e060172. doi: 10.1136/bmjopen-2021-060172.
- Fagundes A Jr, Morrow DA, Oyama K, Furtado RHM, Zelniker TA, Tang M, Kuder JF, Murphy SA, Hamer A, Keech AC, Sever P, Giugliano RP, Sabatine MS, Bergmark BA. Biomarker Prediction of Complex Coronary Revascularization Procedures in the FOURIER Trial. J Am Coll Cardiol. 2022 Aug 30;80(9):887-897. doi: 10.1016/j.jacc.2022.05.051.
- Furtado RHM, Fagundes AA Jr, Oyama K, Zelniker TA, Tang M, Kuder JF, Murphy SA, Hamer A, Wang H, Keech AC, Giugliano RP, Sabatine MS, Bergmark BA. Effect of Evolocumab in Patients With Prior Percutaneous Coronary Intervention. Circ Cardiovasc Interv. 2022 Mar;15(3):e011382. doi: 10.1161/CIRCINTERVENTIONS.121.011382. Epub 2022 Feb 25.
- Oyama K, Giugliano RP, Tang M, Bonaca MP, Saver JL, Murphy SA, Ruzza A, Keech AC, Sever PS, Sabatine MS, Bergmark BA. Effect of evolocumab on acute arterial events across all vascular territories : results from the FOURIER trial. Eur Heart J. 2021 Dec 14;42(47):4821-4829. doi: 10.1093/eurheartj/ehab604.
- Keech AC, Oyama K, Sever PS, Tang M, Murphy SA, Hirayama A, Lu C, Tay L, Deedwania PC, Siu CW, Lira Pineda A, Choi D, Charng MJ, Amerena J, Wan Ahmad WA, Chopra VK, Pedersen TR, Giugliano RP, Sabatine MS; FOURIER Study Group. Efficacy and Safety of Long-Term Evolocumab Use Among Asian Subjects - A Subgroup Analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial. Circ J. 2021 Oct 25;85(11):2063-2070. doi: 10.1253/circj.CJ-20-1051. Epub 2021 May 15.
- Oyama K, Furtado RHM, Fagundes A Jr, Zelniker TA, Tang M, Kuder J, Murphy SA, Hamer A, Wang H, Keech AC, Giugliano RP, Sabatine MS, Bergmark BA. Effect of Evolocumab on Complex Coronary Disease Requiring Revascularization. J Am Coll Cardiol. 2021 Jan 26;77(3):259-267. doi: 10.1016/j.jacc.2020.11.011. Epub 2020 Nov 13.
- Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.
- Deedwania P, Murphy SA, Scheen A, Badariene J, Pineda AL, Honarpour N, Keech AC, Sever PS, Pedersen TR, Sabatine MS, Giugliano RP. Efficacy and Safety of PCSK9 Inhibition With Evolocumab in Reducing Cardiovascular Events in Patients With Metabolic Syndrome Receiving Statin Therapy: Secondary Analysis From the FOURIER Randomized Clinical Trial. JAMA Cardiol. 2021 Feb 1;6(2):139-147. doi: 10.1001/jamacardio.2020.3151.
- Gencer B, Mach F, Murphy SA, De Ferrari GM, Huber K, Lewis BS, Ferreira J, Kurtz CE, Wang H, Honarpour N, Keech AC, Sever PS, Pedersen TR, Sabatine MS, Giugliano RP. Efficacy of Evolocumab on Cardiovascular Outcomes in Patients With Recent Myocardial Infarction: A Prespecified Secondary Analysis From the FOURIER Trial. JAMA Cardiol. 2020 Aug 1;5(8):952-957. doi: 10.1001/jamacardio.2020.0882.
- Bergmark BA, O'Donoghue ML, Murphy SA, Kuder JF, Ezhov MV, Ceska R, Gouni-Berthold I, Jensen HK, Tokgozoglu SL, Mach F, Huber K, Gaciong Z, Lewis BS, Schiele F, Jukema JW, Pedersen TR, Giugliano RP, Sabatine MS. An Exploratory Analysis of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition and Aortic Stenosis in the FOURIER Trial. JAMA Cardiol. 2020 Jun 1;5(6):709-713. doi: 10.1001/jamacardio.2020.0728.
- Wiviott SD, Giugliano RP, Morrow DA, De Ferrari GM, Lewis BS, Huber K, Kuder JF, Murphy SA, Forni DM, Kurtz CE, Honarpour N, Keech AC, Sever PS, Pedersen TR, Sabatine MS. Effect of Evolocumab on Type and Size of Subsequent Myocardial Infarction: A Prespecified Analysis of the FOURIER Randomized Clinical Trial. JAMA Cardiol. 2020 Jul 1;5(7):787-793. doi: 10.1001/jamacardio.2020.0764.
- Giugliano RP, Pedersen TR, Saver JL, Sever PS, Keech AC, Bohula EA, Murphy SA, Wasserman SM, Honarpour N, Wang H, Lira Pineda A, Sabatine MS; FOURIER Investigators. Stroke Prevention With the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Evolocumab Added to Statin in High-Risk Patients With Stable Atherosclerosis. Stroke. 2020 May;51(5):1546-1554. doi: 10.1161/STROKEAHA.119.027759. Epub 2020 Apr 21.
- Charytan DM, Sabatine MS, Pedersen TR, Im K, Park JG, Pineda AL, Wasserman SM, Deedwania P, Olsson AG, Sever PS, Keech AC, Giugliano RP; FOURIER Steering Committee and Investigators. Efficacy and Safety of Evolocumab in Chronic Kidney Disease in the FOURIER Trial. J Am Coll Cardiol. 2019 Jun 18;73(23):2961-2970. doi: 10.1016/j.jacc.2019.03.513.
- Murphy SA, Pedersen TR, Gaciong ZA, Ceska R, Ezhov MV, Connolly DL, Jukema JW, Toth K, Tikkanen MJ, Im K, Wiviott SD, Kurtz CE, Honarpour N, Giugliano RP, Keech AC, Sever PS, Sabatine MS. Effect of the PCSK9 Inhibitor Evolocumab on Total Cardiovascular Events in Patients With Cardiovascular Disease: A Prespecified Analysis From the FOURIER Trial. JAMA Cardiol. 2019 Jul 1;4(7):613-619. doi: 10.1001/jamacardio.2019.0886.
- O'Donoghue ML, Fazio S, Giugliano RP, Stroes ESG, Kanevsky E, Gouni-Berthold I, Im K, Lira Pineda A, Wasserman SM, Ceska R, Ezhov MV, Jukema JW, Jensen HK, Tokgozoglu SL, Mach F, Huber K, Sever PS, Keech AC, Pedersen TR, Sabatine MS. Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk. Circulation. 2019 Mar 19;139(12):1483-1492. doi: 10.1161/CIRCULATIONAHA.118.037184.
- Qamar A, Giugliano RP, Keech AC, Kuder JF, Murphy SA, Kurtz CE, Wasserman SM, Sever PS, Pedersen TR, Sabatine MS. Interindividual Variation in Low-Density Lipoprotein Cholesterol Level Reduction With Evolocumab: An Analysis of FOURIER Trial Data. JAMA Cardiol. 2019 Jan 1;4(1):59-63. doi: 10.1001/jamacardio.2018.4178.
- Martin SS, Giugliano RP, Murphy SA, Wasserman SM, Stein EA, Ceska R, Lopez-Miranda J, Georgiev B, Lorenzatti AJ, Tikkanen MJ, Sever PS, Keech AC, Pedersen TR, Sabatine MS. Comparison of Low-Density Lipoprotein Cholesterol Assessment by Martin/Hopkins Estimation, Friedewald Estimation, and Preparative Ultracentrifugation: Insights From the FOURIER Trial. JAMA Cardiol. 2018 Aug 1;3(8):749-753. doi: 10.1001/jamacardio.2018.1533.
- Sabatine MS, De Ferrari GM, Giugliano RP, Huber K, Lewis BS, Ferreira J, Kuder JF, Murphy SA, Wiviott SD, Kurtz CE, Honarpour N, Keech AC, Sever PS, Pedersen TR. Clinical Benefit of Evolocumab by Severity and Extent of Coronary Artery Disease: Analysis From FOURIER. Circulation. 2018 Aug 21;138(8):756-766. doi: 10.1161/CIRCULATIONAHA.118.034309.
- Bohula EA, Giugliano RP, Leiter LA, Verma S, Park JG, Sever PS, Lira Pineda A, Honarpour N, Wang H, Murphy SA, Keech A, Pedersen TR, Sabatine MS. Inflammatory and Cholesterol Risk in the FOURIER Trial. Circulation. 2018 Jul 10;138(2):131-140. doi: 10.1161/CIRCULATIONAHA.118.034032. Epub 2018 Mar 12.
- Bonaca MP, Nault P, Giugliano RP, Keech AC, Pineda AL, Kanevsky E, Kuder J, Murphy SA, Jukema JW, Lewis BS, Tokgozoglu L, Somaratne R, Sever PS, Pedersen TR, Sabatine MS. Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease: Insights From the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Circulation. 2018 Jan 23;137(4):338-350. doi: 10.1161/CIRCULATIONAHA.117.032235. Epub 2017 Nov 13.
- Sabatine MS, Leiter LA, Wiviott SD, Giugliano RP, Deedwania P, De Ferrari GM, Murphy SA, Kuder JF, Gouni-Berthold I, Lewis BS, Handelsman Y, Pineda AL, Honarpour N, Keech AC, Sever PS, Pedersen TR. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial. Lancet Diabetes Endocrinol. 2017 Dec;5(12):941-950. doi: 10.1016/S2213-8587(17)30313-3. Epub 2017 Sep 15.
- Giugliano RP, Pedersen TR, Park JG, De Ferrari GM, Gaciong ZA, Ceska R, Toth K, Gouni-Berthold I, Lopez-Miranda J, Schiele F, Mach F, Ott BR, Kanevsky E, Pineda AL, Somaratne R, Wasserman SM, Keech AC, Sever PS, Sabatine MS; FOURIER Investigators. Clinical efficacy and safety of achieving very low LDL-cholesterol concentrations with the PCSK9 inhibitor evolocumab: a prespecified secondary analysis of the FOURIER trial. Lancet. 2017 Oct 28;390(10106):1962-1971. doi: 10.1016/S0140-6736(17)32290-0. Epub 2017 Aug 28.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Evolocumab | Monoclonal antibody | 140 mg | Subcutaneous |
| Subject | Evolocumab | Monoclonal antibody | 420 mg | Subcutaneous |